Analysis of vaccine-induced T cells in humans with cancer

Abstract

Over the past several years, progress in the field of tumor immunology has lead to advances in active immunotherapy and vaccination as a means ofeliciting tumor-specific immune responses to mediate tumor regression and clearance. Developing vaccines targeted against cancer became an important focus as a therapy following the success of viral vaccines in preventing infection and disease. In humans with cancer, similar to viral infections, the host immune system is capable of recognizing antigens expressed on tumor cells. This similarity allows the immunological framework of the viral vaccine to be adapted to the cancer setting in hopes of enhancing human T-cell reactivity against tumor. It is generally believed that a requirement for tumor destruction to occur is the induction of sufficient levels of immune cells with high avidity for recognition of tumor antigens. Moreover, the cells must be targeted to the tumor site and be capable of infiltrating tumor stroma.2 Several tumor-associated antigens (TAA) have been identified in the melanoma model which has allowed for immunization trials to evaluate therapeutic potential of tumor-specific T-cell induction. Some clinical trials reported limited success ofT-cell mediated tumor rejection, reportingpartial or complete regression in 10 to 30% of patients. Although tumor regression was not observed following active immunization in vivo, ex vivo assays evaluating TAA-specific T cells demonstrated tumor recognition and subsequent T-cell activation suggesting that tumor-specific T-cell induction indeed occurs but alone is not adequate to induce tumor regression. Recently, the usefulness and success of active-specific immunization (ASI) against TAAs as a means ofeliciting a tumor-specific immune response leading to tumor regression and clearance has been a topic of debate and discussion.